Chiral separation of verapamil and related compounds using micellar electrokinetic capillary chromatography with mixed micelles of bile salt and polyoxyethylene ethers

Abstract

Micellar electrokinetic capillary chromatography (MECC) using surfactant solutions containing sodium deoxycholate (NaDC), polyoxyethylene ethers, and methanol produced simultaneous baseline separation of the enantiomers of verapamil, norverapamil and gallopamil. Studies were conducted to determine the enantiomeric resolution obtained for verapamil and bi-2-naphthol with NaDC solutions, binary mixtures of NaDC with several polyoxyethylene ethers, and ternary mixtures of NaDC, polyoxyethylene ethers and methanol. Experiments were performed to determine the effect of three variables on chiral resolution: (1) the type of ether; (2) the mole fraction of ether in solutions with bile salt; and (3) the percentage of methanol in the mobile phase. The polyoxyethylene ethers studied included polyoxyethylene-8-decyl ether (C 10E 8), polyoxyethylene-6-dodecyl ether (C 12E 6), and polyoxyethylene-4-dodecyl ether (C 12E 4). Simultaneous baseline separation of the enantiomers of verapamil, norverapamil and gallopamil was obtained using a solution containing the ether C 12E 4. The mole fraction of ether was 0.30 and the total surfactant concentration was 50 m M in this solution. The solvent mixture used for this separation was 25% methanol by volume.